Our long-term goal is to elucidate the cellular mechanisms of early visual processing in the mammalian retina. Light-evoked signals, noise, and receptive fields will be characterized in single rods and cones. The results will be related quantitatively to human vision and visual limitations. The overall objective is to determine how photoreceptor response characteristics shape our visual experience. This proposal focuses specifically on the manner in which ions, metabolites, and electrical signals pass directly between photoreceptors through gap junctions. We will determine the strength of gap junctional coupling between the different photoreceptor types, the extent to which coupling strength is modulated by light and voltage, and the endogenous retinal factors that mediate the modulation. We will also use gap junction-specific antibodies and pharmacological agents to elucidate the molecular mechanisms that influence coupling strength. It has been proposed that the degeneration of cones in patients with retinitis pigmentosa and macular degeneration is due to the generation of cytotoxic molecules in dying rods that are transferred into cones by way of rod-cone gap junctions. Elucidation of the mechanisms involved in modulation of photoreceptor coupling and the identification of specific exogenous factors that can block of coupling will be useful in developing new therapies for sparing cone vision in patients with retinal degenerations.